title: Maternal stress and effects of prenatal air pollution on offspring mental health outcomes in mice.
abstract: BACKGROUND
  Low socioeconomic status is consistently associated with reduced physical and mental health, but the mechanisms remain unclear. Increased levels of urban air pollutants interacting with parental stress have been proposed to explain health disparities in respiratory disease, but the impact of such interactions on mental health is unknown.
  
  
  OBJECTIVE
  We aimed to determine whether prenatal air pollution exposure and stress during pregnancy act synergistically on offspring to induce a neuroinflammatory response and subsequent neurocognitive disorders in adulthood.
  
  
  METHODS
  Mouse dams were intermittently exposed via oropharyngeal aspiration to diesel exhaust particles (DEP; 50 μg × 6 doses) or vehicle throughout gestation. This exposure was combined with standard housing or nest material restriction (NR; a novel model of maternal stress) during the last third of gestation.
  
  
  RESULTS
  Adult (postnatal day 60) offspring of dams that experienced both stressors (DEP and NR) displayed increased anxiety, but only male offspring of this group had impaired cognition. Furthermore, maternal DEP exposure increased proinflammatory interleukin (IL)-1β levels within the brains of adult males but not females, and maternal DEP and NR both decreased anti-inflammatory IL-10 in male, but not female, brains. Similarly, only DEP/NR males showed increased expression of the innate immune recognition gene toll-like receptor 4 (Tlr4) and its downstream effector, caspase-1.
  
  
  CONCLUSIONS
  These results show that maternal stress during late gestation increases the susceptibility of offspring-particularly males-to the deleterious effects of prenatal air pollutant exposure, which may be due to a synergism of these factors acting on innate immune recognition genes and downstream neuroinflammatory cascades within the developing brain.
authors.affiliation: Department of Psychology and Neuroscience, Duke University, Durham, North Carolina 27710, USA. jessica.bolton@duke.edu
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Bolton
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Huff
authors.forename: Susan H
authors.initials: SH
authors.lastname: Smith
authors.forename: S Nicholas
authors.initials: SN
authors.lastname: Mason
authors.forename: W Michael
authors.initials: WM
authors.lastname: Foster
authors.forename: Richard L
authors.initials: RL
authors.lastname: Auten
authors.forename: Staci D
authors.initials: SD
authors.lastname: Bilbo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D020170:Caspase 1 / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D060888:Real-Time Polymerase Chain Reaction; D012737:Sex Factors; D013312:Stress, Physiological / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D016207:Cytokines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D001335:Vehicle Emissions; D020170:Caspase 1; D006854:Hydrocortisone